Update on the Diagnostic Pitfalls of Autopsy and Post-Mortem Genetic Testing in Cardiomyopathies

Inherited cardiomyopathies are frequent causes of sudden cardiac death (SCD), especially in young patients. Despite at the autopsy they usually have distinctive microscopic and/or macroscopic diagnostic features, their phenotypes may be mild or ambiguous, possibly leading to misdiagnoses or missed diagnoses. In this review, the main differential diagnoses of hypertrophic cardiomyopathy (e.g., athlete’s heart, idiopathic left ventricular hypertrophy), arrhythmogenic cardiomyopathy (e.g., adipositas cordis, myocarditis) and dilated cardiomyopathy (e.g., acquired forms of dilated cardiomyopathy, left ventricular noncompaction) are discussed. Moreover, the diagnostic issues in SCD victims affected by phenotype-negative hypertrophic cardiomyopathy and the relationship between myocardial bridging and hypertrophic cardiomyopathy are analyzed. Finally, the applications/limits of virtopsy and post-mortem genetic testing in this field are discussed, with particular attention to the issues related to the assessment of the significance of the genetic variants.     

Mining data from intensive care patients

In this paper we describe the application of data mining methods for predicting the evolution of patients in an intensive care unit. We discuss the importance of such methods for health care and other application domains of engineering. We argue that this problem is an important but challenging one for the current state of the art data mining methods and explain what improvements on current methods would be useful. We present a promising study on a preliminary data set that demonstrates some of the possibilities in this area.     

Robustness of VS-MRAC with respect to unmodelled dynamics and external disturbances

A variable structure model reference adaptive controller (VS-MRAC) using only input and output measurements was recently proposed and shown to be globally asymptotically stable with superior transient behaviour and disturbance rejection properties. In this paper a singular perturbation approach is used in order to establish the robustness of the controller in the presence of unmodelled dynamics (parasitics) and disturbances. We develop a new Lyapunov-based technique to analyse the overall system and show that for sufficiently small parasitics the system remains stable and the output error is small in some sense.     

A computational study of LP-based heuristic algorithms for two-dimensional guillotine cutting stock problems

In this paper we develop and compare several heuristic methods for solving the general two-dimensional cutting stock problem. We follow the Gilmore-Gomory column generation scheme in which at each iteration a new cutting pattern is obtained as the solution of a subproblem on one stock sheet. For solving this subproblem, in addition to classical dynamic programming, we have developed three heuristic procedures of increasing complexity, based on GRASP and Tabu Search techniques, producing solutions differing in quality and in time requirements. In order to obtain integer solutions from the fractional solutions of the Gilmore-Gomory process, we compare three rounding procedures, rounding up, truncated branch and bound and the solution of a residual problem. We have coded and tested all the combinations of algorithms and rounding procedures. The computational results obtained on a set of randomly generated test problems show their relative efficiency and allow the potential user to choose from among them, according to the available computing time. Rceived: January 9, 2001 / Accepted: December 10, 2001     

An iterative penalty method for the finite element solution of the stationary Navier-Stokes equations

The objective of this paper is to analyse an iterative procedure for the finite element solution of the Stokes and Navier-Stokes stationary problems. For the latter case, the usual condition on the viscosity and the data that ensures uniqueness is assumed. The method is based on the iterative imposition of the incompressibility condition via penalization. Theoretical and numerical results show that this constraint can be approximated iteratively within the same iterative loop used to deal with the nonlinear term of the equations. Two particular iterative schemes are analysed, namely those based on the Picard and Newton-Raphson algorithms.     

A study of the impact of instability on relative permeability and capillary pressure

Because of the rapid changes in saturation which take place in the immediate vicinity of a displacement front, it is not possible to estimate relative permeabilities over the entire saturation range of interest when using the external-drive method. It is demonstrated in this study that this limitation can be removed, if data from an unstabilized and/ or unstable displacement are used. Furthermore, it is shown that use of such data is permissible, provided: (a) saturation profiles and pressure gradients in both phases can be measured directly; (b) the external-drive theory is modified to account for the existence of capillary pressure gradients; and (c) the analysis is carried out from a Lagrangian rather than a Eulerian point of view.A comparison of relative permeabilities obtained by using the Lagrangian method with those obtained using the conventional (without capillary pressure term) and the modified (with the capillary pressure term) Eulerian methods was undertaken to demonstrate the effect of the neglect of the capillary pressure term on relative permeabilities. Also investigated in this study was the impact of instability on the relative permeability and capillary pressure curves for unstable displacements and the effect of instability on the saturation profiles, fractional flow curves and the residual oil saturation. In addition, the effect of instability on the residual oil saturation was studied.     

Residuated bilattices

We introduce a new product bilattice construction that generalizes the well-known one for interlaced bilattices and others that were developed more recently, allowing to obtain a bilattice with two residuated pairs as a certain kind of power of an arbitrary residuated lattice. We prove that the class of bilattices thus obtained is a variety, give a finite axiomatization for it and characterize the congruences of its members in terms of those of their lattice factors. Finally, we show how to employ our product construction to define first-order definable classes of bilattices corresponding to any first-order definable subclass of residuated lattices.     

Evaluation of Floxuridine Oligonucleotide Conjugates Carrying Potential Enhancers of Cellular Uptake

Conjugation of small molecules such as lipids or receptor ligands to anti-cancer drugs has been used to improve their pharmacological properties. In this work, we studied the biological effects of several small-molecule enhancers into a short oligonucleotide made of five floxuridine units. Specifically, we studied adding cholesterol, palmitic acid, polyethyleneglycol (PEG 1000), folic acid and triantennary N-acetylgalactosamine (GalNAc) as potential enhancers of cellular uptake. As expected, all these molecules increased the internalization efficiency with different degrees depending on the cell line. The conjugates showed antiproliferative activity due to their metabolic activation by nuclease degradation generating floxuridine monophosphate. The cytotoxicity and apoptosis assays showed an increase in the anti-cancer activity of the conjugates related to the floxuridine oligomer, but this effect did not correlate with the internalization results. Palmitic and folic acid conjugates provide the highest antiproliferative activity without having the highest internalization results. On the contrary, cholesterol oligomers that were the best-internalized oligomers had poor antiproliferative activity, even worse than the unmodified floxuridine oligomer. Especially relevant is the effect induced by palmitic and folic acid derivatives generating the most active drugs. These results are of special interest for delivering other therapeutic oligonucleotides.